Mild Neurological Phenotype Associated with Hypomorphic Variants in the Ataxia-Telangiectasia Mutated Gene.
functional studies
kinase activity
mild phenotype
p53‐MCL
variant ataxia‐telangiectasia
Journal
Movement disorders clinical practice
ISSN: 2330-1619
Titre abrégé: Mov Disord Clin Pract
Pays: United States
ID NLM: 101630279
Informations de publication
Date de publication:
Jan 2023
Jan 2023
Historique:
received:
27
07
2022
revised:
02
10
2022
accepted:
29
10
2022
entrez:
27
1
2023
pubmed:
28
1
2023
medline:
28
1
2023
Statut:
epublish
Résumé
Ataxia-telangiectasia (A-T) is a progressive multisystemic neurodegenerative disease. The phenotypic spectrum includes conditions (variant A-T) with mild, late-onset, and atypical clinical presentations characterized by the prevalence of dyskinetic rather than ataxic features. We describe the clinical presentations of 3 siblings with early-onset truncal ataxia without obvious neurological deterioration or biological markers of classic A-T phenotype. We performed functional and genetic evaluation of 3 siblings with very mild neurological phenotype. Genetic evaluation with a next-generation sequencing panel for genes causative of cerebellar ataxia detected 2 known ATM gene variants, missense c.9023G>A p.(Arg3008His), and leaky splicing c.1066-6T>G variants. Functional studies showed mildly reduced ATM expression and residual kinase activity in the probands compared with healthy controls. These results suggest the importance of investigating ATM variants even in the presence of clinical and biological atypical cases to ensure specific therapeutic regimens and oncological surveillance in these patients.
Sections du résumé
Background
UNASSIGNED
Ataxia-telangiectasia (A-T) is a progressive multisystemic neurodegenerative disease. The phenotypic spectrum includes conditions (variant A-T) with mild, late-onset, and atypical clinical presentations characterized by the prevalence of dyskinetic rather than ataxic features.
Cases
UNASSIGNED
We describe the clinical presentations of 3 siblings with early-onset truncal ataxia without obvious neurological deterioration or biological markers of classic A-T phenotype. We performed functional and genetic evaluation of 3 siblings with very mild neurological phenotype. Genetic evaluation with a next-generation sequencing panel for genes causative of cerebellar ataxia detected 2 known ATM gene variants, missense c.9023G>A p.(Arg3008His), and leaky splicing c.1066-6T>G variants. Functional studies showed mildly reduced ATM expression and residual kinase activity in the probands compared with healthy controls.
Conclusions
UNASSIGNED
These results suggest the importance of investigating ATM variants even in the presence of clinical and biological atypical cases to ensure specific therapeutic regimens and oncological surveillance in these patients.
Identifiants
pubmed: 36704080
doi: 10.1002/mdc3.13618
pii: MDC313618
pmc: PMC9847291
doi:
Types de publication
Case Reports
Langues
eng
Pagination
124-129Informations de copyright
© 2022 International Parkinson and Movement Disorder Society.
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